CN1480192A - Medication for treating cancer and chronic hepatitis B and its prepn. method - Google Patents
Medication for treating cancer and chronic hepatitis B and its prepn. method Download PDFInfo
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Abstract
A Chinese medicine for treating cancer and hepatitis B is prepared from astragalus root, ginseng and kurarnol. Its advantages are sure curative effect, quickly taking its effect and no toxic by-effect.
Description
Affiliated technical field
The present invention relates to a kind of medicine for the treatment of cancer and chronic hepatitis B, being specifically related to a kind of is the Chinese patent medicine of feedstock production with Chinese medicine, the invention still further relates to the preparation method of this medicine.
Background technology
Although medical research has very big progress, cancer still is human underlying cause of death.Position difference according to morbidity has: hepatocarcinoma, pulmonary carcinoma, rectal cancer, malignant lymphoma, gynecologic malignant tumor etc., the conventional method of treatment of cancer such as operation, chemotherapy, radiotherapy and interventional therapy, just cure the symptoms, not the disease, patient is brought very big misery, also normal cell is killed in kill cancer cell, cause people's immunologic function degression, therapeutic effect is not so good, cure rate is low, and many tumors have resistance and bigger side effect to these conventional Therapeutic Method.
Hepatitis B is a kind of spreading venereal diseases that is caused by hepatitis B virus (Hepatitis B Virus is called for short HBV).China is the high popular district of hepatitis B, has the crowd above 40% infected by HBV, and it is chronic HbsAg carrier that population more than 100,000,000 is arranged.According to investigations, the patient that chronic hepatitis B is now suffered from by China surpasses 3,000 ten thousand people, is subjected to the chronically infected crowd of HBV easily to suffer from primary hepatocarcinoma.The pathogeny of chronic hepatitis B is owing to the disorder of patient's immunoloregulation function, and the machine of can not regulating well can not get removing to HBV, and hepatocyte is subjected to infringement in various degree, hbv replication.The medicine that occurs the treatment chronic hepatitis B in recent years both at home and abroad, clinical efficacy differs, and is recognized that INF-α both at home and abroad, but the negative conversion rate of HbeAg and HBV DNA also only is about 40%, the curative effect far from ideal, and make clinical being restricted owing to certain side effect being arranged and costing an arm and a leg.Lack anti-HBV determined curative effect in the market, the medicine that has no side effect again.
Summary of the invention
Technical problem to be solved by this invention, providing a kind of is the medicine of raw material treatment primary hepatocarcinoma, pulmonary carcinoma, rectal cancer, malignant lymphoma, gynecologic malignant tumor and the chronic hepatitis B made with Chinese medicine, its effective ingredient is clear and definite, quality controllable, use the anticancer and anti-HBV determined curative effect of medicine of the present invention, have no side effect and resistance;
Another technical problem to be solved by this invention provides the preparation method of this medicine, and this preparation method is with respectively distinguish the flavor of effective ingredient in the medicine of abundant extraction, and adopts advanced pharmaceutical formulation.
The technical solution adopted for the present invention to solve the technical problems:
A kind of medicine for the treatment of cancer and chronic hepatitis B is the medicament of being made by the following weight Chinese medicinal raw materials:
Radix Astragali 270-330, Radix Ginseng 90-110, kurarinone 6-12.
The medicine of above-mentioned treatment cancer and chronic hepatitis B is characterized in that: the contained effective ingredient of described medicament forms and part by weight is:
Astragaloside 0.05～0.32, ginsenoside Rg
1+ Re 0.12～0.65, total polysaccharides 2.1～20, kurarinone 6～12.
The above-mentioned medicine that is used for the treatment of cancer and chronic hepatitis B can be made said multiple dosage form on the pharmaceutics, as injection, infusion solutions, lyophilized injectable powder, oral liquid, capsule or tablet.
Above-mentioned materials of weight proportions is made the method for medicine of the present invention, may further comprise the steps:
(1) get Radix Ginseng, extract 1～4 time with 70～90% alcohol heating reflux, each 1～3 hour, medicine residues of Radix Ginseng was standby; Extracting solution merges, behind the most ethanol of reclaim under reduced pressure, add 1～2 times of water gaging, stir evenly, cold preservation 12～48 hours, filter macroporous adsorption resin chromatography post on the filtrate, water and 50～70% ethanol elution successively, collect 50～70% ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.10～1.20 (60 ℃), drying, Radix Ginseng extract.
(2) get the Radix Astragali and medicine residues of Radix Ginseng, decoct with water 1～3 time, each 1～3 hour, collecting decoction filtered, and it is 1.10～1.20 (60 ℃) that filtrate decompression is concentrated into relative density, added ethanol and made and contain the alcohol amount and reach 75%, and cold preservation 12～48 hours precipitates standby; Supernatant reclaim under reduced pressure and to be concentrated into relative density be 1.10～1.20 (60 ℃), add 1～2 times of water gaging, stir evenly, filter macroporous adsorption resin chromatography post on the filtrate, wash with water earlier to eluent colourless till, the ethanol elution of reuse 60～80% is collected ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.10～1.20 (60 ℃), drying gets Radix Astragali extract.
(3) get precipitation under above-mentioned (2), the water dissolution that adds 2～6 times of amounts, filter, filtrate is 100,000 membrane ultrafiltration with molecular weight, and ultrafiltrate reuse molecular weight is that 3000 membrane ultrafiltration is concentrated, concentrated solution adds ethanol to be made and contains alcohol amount and reach 80%, cold preservation filters, and precipitation is washed the final vacuum drying with small amount of ethanol, pulverize, get total polysaccharides.
(4) get Radix Ginseng extract, Radix Astragali extract, total polysaccharides and kurarinone, add water for injection and pharmaceutic adjuvant, stirring and dissolving, sodium hydroxide solution with 10～40% is transferred pH6～7, left standstill 12～48 hours, and filtered, filtrate is made injection by the preparation common process, comprise injection, infusion solutions, injectable powder, promptly make injection of the present invention.
Pharmaceutic adjuvant of the present invention is one or more in sodium chloride, mannitol, 30 POVIDONE K 30 BP/USP 30, glucose, the lactose.
Raw material used in the present invention---the Radix Astragali and Radix Ginseng require to meet respectively " relevant every regulation under the Radix Astragali and the Radix Ginseng item under item of Chinese pharmacopoeia version in 2000; Kurarinone then requires the content of its oxymatrine to be higher than 85%.
The effective ingredient astragaloside of medicine of the present invention and the content detection of oxymatrine have adopted thin layer chromatography scanning, and colorimetry, ginsenoside Rg are adopted in the detection of total polysaccharides
1The content detection of+Re then adopts high-efficient liquid phase technique.Beneficial effect of the present invention:
1, the present invention is made by the Radix Astragali, Radix Ginseng, kurarinone three herbal medicines, wherein contains Radix Astragali saponin, polysaccharide, flavonoid, choline, betanin etc. in the Radix Astragali, and Radix Astragali saponin and astragalus polysaccharides are most important physiologically active ingredient in the Radix Astragali; Radix Ginseng contains chemical constituents such as ginsenoside and ginseng polysaccharide, is most important physiologically active ingredient in the Radix Ginseng; Kurarinone is oxymatrine (C
15H
24N
2O
2).Therefore preparation method of the present invention is according to the character and the pharmacological action of the contained effective ingredient of each Chinese medicine, select for use water and ethanol as extracting solvent, and carry out the purification process extracting solution with macroporous adsorbent resin and ultrafiltration, with the effective ingredient in the refining medicine of respectively distinguishing the flavor of of abundant extraction, thereby medicine of the present invention has clear and definite, the quality controllable characteristics of active ingredient.
2, dosage form of the present invention is an injection, comprises injection, infusion solutions, lyophilized injectable powder, can be directly used in intravenous injection, thereby onset is rapid, bioavailability is high, definite effect is reliable.
3, medicine of the present invention studies show that through stability test, is valid up to 2.5 years, and indexs such as clarity, hemolytic, color and luster, pH value, thermal source, zest all meet " the regulation of the relevant injection of Chinese pharmacopoeia.
4, lyophilized injectable powder of the present invention still has and stores convenient, easy to carry and use advantage except that having the injection characteristics.
5, show that through clinical principium test medicine of the present invention has QI invigorating to be set upright, the enhancing human body immunity function can kill cancer cell, HBV is had remove or suppress it and duplicate effect, and leukocyte increasing is evident in efficacy, does not find obvious toxic-side effects as yet.
The present invention is further illustrated below by embodiment and Pharmacodynamic test of active extract.The preparation of embodiment 1 lyophilized injectable powder
(1) get Radix Ginseng 100g, extract 4 times with 75% alcohol heating reflux, each 1 hour, medicine residues of Radix Ginseng was standby; Extracting solution merges, behind the most ethanol of reclaim under reduced pressure, add 1.5 times of water gagings, stir evenly, cold preservation 42 hours, filter macroporous adsorption resin chromatography post on the filtrate, water and 60% ethanol elution successively, collect 600% ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.18 (60 ℃), drying, Radix Ginseng extract.
(2) get Radix Astragali 315g and medicine residues of Radix Ginseng, decoct with water 3 times, each 1.5 hours, collecting decoction filtered, and it is 1.12 (60 ℃) that filtrate decompression is concentrated into relative density, added ethanol and made and contain the alcohol amount and reach 75%, and cold preservation 40 hours precipitates standby; Supernatant reclaim under reduced pressure and to be concentrated into relative density be 1.16 (60 ℃), add 2 times of water gagings, stir evenly, filter macroporous adsorption resin chromatography post on the filtrate, wash with water earlier to eluent colourless till, the ethanol elution of reuse 65% is collected ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.17 (60 ℃), drying gets Radix Astragali extract.
(3) get precipitation under above-mentioned (2), the water dissolution that adds 5 times of amounts, filter, filtrate is 100,000 membrane ultrafiltration with molecular weight, and ultrafiltrate reuse molecular weight is that 3000 membrane ultrafiltration is concentrated, concentrated solution adds ethanol to be made and contains alcohol amount and reach 80%, cold preservation filters, and precipitation is washed the final vacuum drying with small amount of ethanol, pulverize, get total polysaccharides.
(4) get Radix Ginseng extract, Radix Astragali extract, total polysaccharides and kurarinone 11g, add water for injection 500ml and sodium chloride 1g, mannitol 7g, 30 POVIDONE K 30 BP/USP 30 2g, stirring and dissolving, sodium hydroxide solution with 40% is transferred pH6～7, leaves standstill 38 hours, filters, filtrate is sub-packed in the sterilized cillin bottle, lyophilization, tamponade, gland promptly make lyophilized injectable powder of the present invention.
The preparation of embodiment 2 injection
(1) get Radix Ginseng 110g, extract 3 times with 70% alcohol heating reflux, each 2 hours, medicine residues of Radix Ginseng was standby; Extracting solution merges, behind the most ethanol of reclaim under reduced pressure, add 2 times of water gagings, stir evenly, cold preservation 48 hours, filter macroporous adsorption resin chromatography post on the filtrate, water and 60% ethanol elution successively, collect 60% ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.20 (60 ℃), drying, Radix Ginseng extract.
(2) get Radix Astragali 300g and medicine residues of Radix Ginseng, decoct with water 3 times, each 2 hours, collecting decoction filtered, and it is 1.15 (60 ℃) that filtrate decompression is concentrated into relative density, added ethanol and made and contain the alcohol amount and reach 75%, and cold preservation 48 hours precipitates standby; Supernatant reclaim under reduced pressure and to be concentrated into relative density be 1.18 (60 ℃), add 2 times of water gagings, stir evenly, filter macroporous adsorption resin chromatography post on the filtrate, wash with water earlier to eluent colourless till, the ethanol elution of reuse 60% is collected ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.15 (60 ℃), drying gets Radix Astragali extract.
(3) get precipitation under above-mentioned (2), the water dissolution that adds 6 times of amounts, filter, filtrate is 100,000 membrane ultrafiltration with molecular weight, and ultrafiltrate reuse molecular weight is that 3000 membrane ultrafiltration is concentrated, concentrated solution adds ethanol to be made and contains alcohol amount and reach 80%, cold preservation filters, and precipitation is washed the final vacuum drying with small amount of ethanol, pulverize, get total polysaccharides.
(4) get Radix Ginseng extract, Radix Astragali extract, total polysaccharides and kurarinone 10g, add water for injection 995ml and sodium chloride 2g, stirring and dissolving, sodium hydroxide solution with 40% is transferred pH6～7, leaves standstill 48 hours, filters, filtrate filters with the filter membrane of 0.45um and 0.22um respectively again, the filtrate embedding is in the ampoule of 10ml, and sterilization, quality inspection promptly make injection of the present invention.
The preparation of embodiment 3 infusion solutionses
(1) gets Radix Astragali 320g, Radix Ginseng 105g, kurarinone 10g, prepare Radix Ginseng extract, Radix Astragali extract, total polysaccharides respectively with (1) (2) (3) under 2 of the embodiment.
(2) get above-mentioned Radix Ginseng extract, Radix Astragali extract, total polysaccharides and kurarinone 11g, add water for injection 2000ml and sodium chloride 15g, stirring and dissolving, sodium hydroxide solution with 40% is transferred pH6～7, leaves standstill 40 hours, filters, filtrate filters with the filter membrane of 0.45um and 0.22um respectively again, the filtrate embedding is in the 100ml infusion bottle, and sterilization, quality inspection promptly make infusion solution of the present invention.The main pharmacodynamics test
First's freeze-dried powder antitumor of the present invention pharmacology effect experimentation one, test material 1 medicine and reagent
Lyophilized powder of the present invention: the proud company by the sky, Guangdong provides specification: the 0.3g/ bottle.
KANGLAITE ZHUSHEYE, specification: 10g/100ml, lot number: 0001212-2, KANGLAITE ZHUSHEYE pharmaceutcal corporation, Ltd in Zhejiang produces.Interleukin II (IL-2) injection, specification: 200,000 U/ prop up, and Ke Xing biotech company in Shenzhen produces.IL-2 and α-Zhong Liuhuaisiyinzi (TNF-α) test kit, concanavalin A (Con-A, 1g/ bottle) are available from crystalline substance U.S. bio-engineering corporation.2. experimental animal
Cleaning level kunming mice, body weight 20 ± 2g, in 8 ages in week, male and female half and half provide (Guangdong probatio inspectionem pecuoarem word 2000A058 number) by No.1 Military Medical Univ.'s Experimental Animal Center.Mice male and female sub-cage rearing, is freely drunk water 25 ± 1 ℃ of room temperatures, relative humidity 50%-70% by 5/cage.Raise after 3 days, get outward appearance, appetite, the N/R mice of defecation and test.Other
Mice SRS-82 cell strain is available from Shanghai cell biological institute; Two, experimental technique and result's 1 lyophilized powder of the present invention are to the inhibition test 1.1 experimental technique mice group of lotus SRS-82 sarcoma mice: mice is divided into totally 6 groups of blank groups, model group, lyophilized powder 50mg/kg of the present invention, 100mg/kg, 200mg/kg group, KANGLAITE ZHUSHEYE injection group, 20 of every group of mices are repeated 2 times.
Tumor inoculation: with behind the SRS-82 cell inoculation kunming mice of cultivating the 8th day, extract the about 15ml of ascites in 4 mouse peritoneals respectively, being diluted to cell number with normal saline is 1.0 * 10
7Behind/the ml (30ml altogether), every mice left side groin subcutaneous injection 0.2ml (2.0 * 10
6/ only).
Administering mode and time: every mouse peritoneal injection (ip) administration 0.1ml/10g, KANGLAITE ZHUSHEYE is not diluted direct ip administration, the beginning administration in the 2nd day behind inoculated tumour, 1 time/day, totally 10 days.
Tumour inhibiting rate: in postvaccinal the 12nd day, take off cervical vertebra execution and respectively organize mice, peel off tumor mass, take by weighing tumor weight, and calculate tumour inhibiting rate as follows:
The inhibitory action of tumour inhibiting rate=(model group average tumor weight-administration group average tumor weight)/model group average tumor weight * 1.2 pairs of tumors of 100%1.2 experimental results
Compare with model group, lyophilized powder of the present invention has the obvious suppression effect to lotus SRS-82 tumor mouse tumor, and be dose-effect relationship, the average tumour inhibiting rate about 55% of three advance copy invention high dose group, be better than in the dosage group 33% and low dose group 21%, a little more than KANGLAITE ZHUSHEYE 47%, be starkly lower than the tumour inhibiting rate of high dose group of the present invention, see Table 1:
Table 1 lyophilized powder of the present invention injects 50.0 53.9 59.6 54.5 ± 6.7 to average tumour inhibiting rate comparison (%) group test 1 test 2 tests 3 average lyophilized powder high doses of the present invention of lotus SRS-82 tumor mouse tumor
▲Dosage injects 31.6 49.2 19.2 33.3 ± 15.0 in the lyophilized powder of the present invention
☆Lyophilized powder low dosage of the present invention is injected 28.9 20.3 13.5 20.9 ± 7.6 KANGLAITE ZHUSHEYE and is injected 46.5 35.9 51.9 44.8 ± 8.2
★Compare with high dose group,
★P＜0.01;
☆P＜0.05.2. lyophilized powder of the present invention is to the influence of lotus SRS-82 sarcoma effect of immunologic function 2.1 method 2.1.1 lyophilized powder of the present invention to liver, spleen, thymic weight
Behind inoculated tumour the 12nd day, disconnected neck is put to death and is respectively organized mice, takes by weighing the body weight of every mice and liver, spleen, thymic weight respectively, calculates liver, spleen, thymus coefficient.2.1.2 quantity of leucocyte of the present invention changes
Solid tumor mice the 11st day behind inoculated tumour, eye socket rear vein beard about 100 μ l that take a blood sample detect the leukocyte count of respectively organizing mice with Japanese F-800 hemocyte automatic analyzer.2.1.3 the macrophages in vitro phagocytic function detects
Each organizes white mice in the cold DMEM culture medium of experiment the 11st day difference intraperitoneal injection 5ml, and peritoneal fluid is extracted in soft abdominal cavity out behind the 10min, and the centrifugal 10min of 1000r/min abandons the part supernatant, stays about 2ml.Add 1% Sanguis Gallus domesticus ball 2ml then behind the mixing.Put in the constant incubator behind the 60min, the mixing smear, Wright's staining calculates 100 macrophage phagocytic percentage rate (what cytophagies erythrocyte) and phagocytic index (having engulfed what erythrocyte altogether).2.1.4 the NK cytoactive is measured
Effector lymphocyte's preparation is with method 5.4.With the HepG2 cell that went down to posterity a day, wash once with DMEM work culture medium, being prepared into whole suspension cell concentration is 5.0 * 10
5/ ml is target cell.Imitating the target ratio is 50: 1.Get 96 well culture plates, every pipe is established 3 multiple holes, establishes DMEM work medium controls and HepG2 cell/work medium controls simultaneously, and except that these two groups, all the other are respectively organized every hole and add 100 μ l effector lymphocytes and 100 μ l target cells, put 37 ℃ of 5%CO
2Hatch 48h in the incubator and take out, the centrifugal 10min of 1000r/min, every hole is drawn supernatant 100 μ l and is discarded, and adds MTT liquid 10 μ l again, continue to cultivate 4h and take out, every hole adds 100 μ l 0.1%SDS solution, hatches 2h again, take out, room temperature is placed 30min, measures each hole A with Model 450 microplate reader
570nmValue is calculated as follows the NK cytoactive.
NK cytoactive (%)=(1-experimental port A
570nm/ control wells A
570nm) * 100%2.1.5 tumor-bearing mice serum il-2 and TNF Determination on content
Behind tumor inoculation the 12nd day, by the blood sampling of eye socket rear vein beard, the centrifugal 10min separation of serum of 3000r/min was with mice IL-2 and the TNF-α kit measurement serum il-2 and the TNF-alpha levels of brilliant U.S. bio-engineering corporation.2.2 2.2.1 lyophilized powder of the present invention is to the influence of liver, spleen, thymus as a result
Lyophilized powder of the present invention sees Table 2 to the influence of lotus SRS-82 sarcoma Mouse Liver, spleen, thymus coefficient.With model group relatively, after the lyophilized powder administration of the present invention, the spleen coefficient obviously reduces (p＜0.05), liver, thymus index variation not obvious (low dose group liver less than model group, P＜0.01).
Table 2 lyophilized powder of the present invention is to influence (x+S) group number of mice liver coefficient spleen coefficient thymus coefficient blank 20 7.55 ± 2.56 1.93 ± 1.34 2.07 ± 1.58 models 16 9.24 ± 1.69 of SRS-82 solid tumor mice part organ coefficient
#2.61 ± 1.49
#2.66 ± 0.79 lyophilized powder high dose 18 9.70 ± 2.66* 2.01 ± 0.51 of the present invention
△2.77 dosage 19 7.97 in ± 1.17 lyophilized powders of the present invention ± 1.62 1.86 ± 0.47
△2.27 ± 0.78
#Lyophilized powder low dosage 20 7.38 ± 1.24 of the present invention
▲1.87 ± 0.62
△2.38 ± 0.93
#KANGLAITE ZHUSHEYE 16 8.35 ± 2.01 1.85 ± 0.76
△2.65 ± 1.55 with the blank group relatively, * P＜0.01,
#P＜0.05; Compare with model group,
▲P＜0.01,
△P＜0.05.2.2.2 lyophilized powder of the present invention is to the influence of tumor-bearing mice blood leukocytes
Lyophilized powder of the present invention sees Table 3 to the influence of lotus SRS-82 tumor mice blood leukocytes number, and the blood leukocytes number of visible tumor-bearing mice raises, and is the most obvious with lyophilized powder height of the present invention, middle dosage group Mus.
(the 12nd day, x+S) group mice quantity leukocyte count (* 10 to the influence of lotus SRS-82 tumor mice blood leukocytes for table 3 lyophilized powder of the present invention
9/ L) blank 20 7.05 ± 0.83 model 16 8.91 ± 1.43 lyophilized powder high dose 18 11.59 ± 4.07* of the present invention
△Dosage 19 10.91 ± 5.36 in the lyophilized powder of the present invention
#Lyophilized powder low dosage 18 7.50 ± 3.75 KANGLAITE ZHUSHEYE 16 7.54 ± 0.77 of the present invention compare with the blank group, * P＜0.01,
#P＜0.05; Compare with model group,
△P＜0.05.2.2.3 macrophages in vitro phagocytic function detects
Lyophilized powder of the present invention sees Table 4 to the influence of lotus SRS-82 tumor macrophage phagocytosis of mice, during the phagocytic rate of visible high dose group and phagocytic index all are higher than, low dose group.
Table 4 lyophilized powder of the present invention is to the influence of tumor-bearing mice macrophage phagocytic function (n=8, group phagocytic rate phagocytic index blank 0.43 ± 0.18 0.58 ± 0.20 model 0.43 ± 0.15 0.60 ± 0.18 lyophilized powder high dose 0.58 of the present invention ± 0.14 0.80 ± 0.21 of x ± s)
# △Dosage 0.48 in the lyophilized powder of the present invention ± 0.11 0.70 ± 0.13 lyophilized powder low dosage 0.32 of the present invention ± 0.08 0.70 ± 0.17 KANGLAITE ZHUSHEYE 0.48 ± 0.08 0.85 ± 0.20*
▲Compare with the blank group, * P＜0.01,
#P＜0.05; Compare with model group,
▲P＜0.01,
△P＜0.05.2.2.3 NK cytoactive measurement result
Activity test the results are shown in Table 5 (every group of 11-12 mices) to lyophilized powder of the present invention to lotus SRS-82 tumor NK cells in mice, except that model group and low dose group of the present invention low (about 25%), and all the other each NK cytoactives similar (about 35%) of organizing.
Table 5 freeze-dried powder of the present invention affects group 123456789 10 11 12 x ± S blank 0.33 0.32 0.37 0.37 0.21 0.25 0.19 0.32 0.38 0.33 0.33 0.46 0.32 ± 0.08 model 0.32 0.20 0.31 0.27 0.21 0.26 0.25 0.32 0.19 0.31 0.15 0.22 0.25 ± 0.06 to tumor-bearing mice NK cytoactive#Lyophilized powder high dose 0.45 0.38 0.30 0.43 0.37 0.43 0.35 0.41 0.34 0.34 0.34 0.24 0.37 ± 0.06 of the present invention
▲Dosage 0.47 0.37 0.26 0.31 0.31 0.30 0.26 0.34 0.30 0.35 0.44 0.45 0.35 ± 0.07 in the lyophilized powder of the present invention
▲Lyophilized powder low dosage 0.33 0.28 0.30 0.31 0.09 0.19 0.18 0.26 0.27 0.32 0.31 0.20 0.25 ± 0.07 of the present invention
#KANGLAITE ZHUSHEYE 0.36 0.38 0.29 0.36 0.40 0.36 0.33 0.35 0.46 0.41 0.50 0.38 ± 0.06
# ▲Compare with the blank group,
#P＜0.05; Compare with model group,
▲P＜0.01. (numerical value is the meansigma methods in each sample 3 hole in the table) 2.2.4 tumor-bearing mice serum il-2 and TNF Determination on content result
Lyophilized powder of the present invention sees Table 6 to the influence of lotus SRS-82 tumor mice serum TNF and IL-2 level, it is similar that the result respectively organizes the TNF level of mice, but serum il-2 level of high dose group of the present invention and KANGLAITE ZHUSHEYE injection group raises, and is higher than dosage among the present invention, low dose group.
Table 6 lyophilized powder of the present invention is to the influence of tumor-bearing mice serum TNF, IL-2 level (n=11, group TNF-α IL-2 blank 0.030 ± 0.016 0.068 ± 0.020 model 0.025 ± 0.015 0.043 ± 0.015* high dose 0.025 of the present invention ± 0.020 0.107 ± 0.025* of x ± s)
▲Dosage 0.024 among the present invention ± 0.018 0.085 ± 0.023
▲Low dosage 0.024 of the present invention ± 0.016 0.065 ± 0.030
△KANGLAITE ZHUSHEYE 0.024 ± 0.014 0.101 ± 0.029*
▲Compare * P＜0.01 with the blank group; Compare with model group,
▲P＜0.01,
△P＜0.05.
Experimentation 1. experiment materials 1.1 medicines of second portion lyophilized powder anti-hepatitis virus of the present invention:
Lyophilized powder of the present invention: the 0.3g/ bottle is provided by the proud company in sky, Guangdong.
Draw miaow furan fixed (3TC) to produce lot number 0112005 by Glaxo Wellcome (Suzhou) pharmaceutical Co. Ltd.1.2 animal:
Male age in days Longyan sheldrake, available from hatchery, village, Shi Jing Chaoyang, Guangzhou, about 100 grams of body weight during experiment/only, the conventional raising.1.3 main agents and instrument
The NC film is available from Amersham company.The DHBV plasmid is extracted by the traditional Chinese medical science coyote hole technical staff of Institute for Tropical Diseases of Traditional Chinese Medicine University Of Guangzhou.
The nick translation medicine box is available from promega company.α-
32P-dCTP is available from the inferior brightness in Beijing company.
Sephadex G-50 is available from Pharmacia company.
96 holes hybridization sample applicator: U.S. Bio-rad company product.
Geiger counter: U.S. S.E.International company product.1.4 positive drug is selected:
Select the stronger miaow furan that draws of anti-HBV effect to have positive contrast medicine made to order.1.5 result treatment: carry out statistical procedures with one factor analysis of variance.The experiment of 2 experimental techniques and result's 2.1 anti-congenital infection dhbv dna effects
One age in days Longyan sheldrake is bought the same day back and is got blood in the shin vein, and behind the separation of serum, with the method detection DHBV of dot blot hybridization, the duck of selecting congenital infection experimentizes, the about 100g of duck average weight.The present invention of administration group divides 40mg/kg, 80mg/kg, three dosage groups of 160mg/kg; The intravenous injection volume is 0.4ml/, every day 1 time; Other establishes the virus control group, intravenous injection NS; Positive drug is selected for use and is drawn fixed (3TC) 20mg/kg of miaow furan, oral 1ml/, every day 1 time; Be 10 days one courses of treatment.(T before medication
0), the 5th day (T of medication
5), the 10th day (T
10) and drug withdrawal after the 3rd day (P
3), get blood from duck lower limb shin vein, separation of serum ,-70 ℃ are frozen to be checked.
The DHBV-DNA detection method:
It is clear to get above-mentioned Sanguis Anas domestica, and every batch with the time point film, measure Sanguis Anas domestica clear in the variation of DHBV-DNA level, press nick translation test kit description method, usefulness
32P labelling DHBV-DNA probe, and make the clear dot blot hybridization of Sanguis Anas domestica, autoradiography diaphragm speckle is measured OD value (the optical filter wavelength is 490nm) on enzyme mark detector, calculate serum DHBV-DNA density.The result takes the administration different time (T of medicine group
5, T
10, P
3) with administration before (T
0) compare, and the identical time with matched group of medicine group compares.The results are shown in Table 1.
Table 1 the present invention in the duck body to the inhibitory action of DHBV-DNA (x ± s)
Duck is counted OD
490Value group dosage
(n) T
0T
5T
10P
3Virus control-7 2.12 ± 0.52 2.08 ± 0.47 1.94 ± 0.51 1.53 ± 0.47*3TC 20mg/kg 8 1.88 ± 0.66 0.62 ± 0.63
* △ △0.39 ± 0.47
* △ △2.22 ± 0.70 40mg/kg 5 2.15 of the present invention ± 0.21 1.95 ± 0.41 1.51 ± 0.52 1.44 ± 0.20*
80mg/kg 7 1.89±0.18 1.22±0.55** 1.01±0.58* 1.42±0.38**
160mg/kg 6 2.21±0.54 0.78±0.47** 0.58±0.12** 1.05±0.26**
(T before medicine group administration different time and the administration
0) relatively: * P＜0.05 * * P＜0.01
The identical time ratio with matched group of medicine group is:
△ △P＜0.01
Show that by table 1 three dosage groups of lyophilized powder of the present invention have obvious inhibitory action to DHB 10 day course of treatment.3TC also acts on significantly (P＜0.01).
Claims (6)
1, a kind of medicine for the treatment of cancer and chronic hepatitis B is characterized in that: it is the medicament of being made by the following weight proportion raw material:
Radix Astragali 270-330, Radix Ginseng 90-110, kurarinone 6-12.
2, the medicine of treatment cancer according to claim 1 and chronic hepatitis B is characterized in that: contained effective ingredient of described medicament and weight portion thereof are:
Astragaloside 0.05～0.32, ginsenoside Rg
1+ Re 0.12～0.65, total polysaccharides 2.1～20, kurarinone 6～12.
3, the medicine of treatment cancer according to claim 1 and 2 and chronic hepatitis B is characterized in that: described medicament is a said dosage form on any pharmaceutics.
4, the medicine of treatment cancer according to claim 3 and chronic hepatitis B, it is characterized in that: described medicament is an injection, comprises injection, infusion solutions, lyophilized injectable powder.
5, the preparation method of the medicine of each described treatment cancer of claim 4 and chronic hepatitis B may further comprise the steps:
(1) get Radix Ginseng, extract 1～4 time with 70～90% alcohol heating reflux, each 1～3 hour, medicine residues of Radix Ginseng was standby; Extracting solution merges, behind the most ethanol of reclaim under reduced pressure, add 1～2 times of water gaging, stir evenly, cold preservation 12～48 hours, filter macroporous adsorption resin chromatography post on the filtrate, water and 50～70% ethanol elution successively, collect 50～70% ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.10～1.20 (60 ℃), drying, Radix Ginseng extract.
(2) get the Radix Astragali and medicine residues of Radix Ginseng, decoct with water 1～3 time, each 1～3 hour, collecting decoction filtered, and it is 1.10～1.20 (60 ℃) that filtrate decompression is concentrated into relative density, added ethanol and made and contain the alcohol amount and reach 75%, and cold preservation 12～48 hours precipitates standby; Supernatant reclaim under reduced pressure and to be concentrated into relative density be 1.10～1.20 (60 ℃), add 1～2 times of water gaging, stir evenly, filter macroporous adsorption resin chromatography post on the filtrate, wash with water earlier to eluent colourless till, the ethanol elution of reuse 60～80% is collected ethanol elution, reclaim under reduced pressure and to be concentrated into relative density be 1.10～1.20 (60 ℃), drying gets Radix Astragali extract.
(3) get precipitation under above-mentioned (2), the water dissolution that adds 2～6 times of amounts, filter, filtrate is 100,000 membrane ultrafiltration with molecular weight, and ultrafiltrate reuse molecular weight is that 3000 membrane ultrafiltration is concentrated, concentrated solution adds ethanol to be made and contains alcohol amount and reach 80%, cold preservation filters, and precipitation is washed the final vacuum drying with small amount of ethanol, pulverize, get total polysaccharides.
(4) get Radix Ginseng extract, Radix Astragali extract, total polysaccharides and kurarinone, add water for injection and pharmaceutic adjuvant, stirring and dissolving, sodium hydroxide solution with 10～40% is transferred pH6～7, left standstill 12～48 hours, filter, filtrate is made injection by the preparation common process, comprises injection, infusion solutions, lyophilized injectable powder.
6, the process for preparing medicine of treatment cancer according to claim 5 and chronic hepatitis B is characterized in that: described pharmaceutic adjuvant is one or more in sodium chloride, mannitol, 30 POVIDONE K 30 BP/USP 30, glucose, the lactose.
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| CNA031397913A CN1480192A (en) | 2003-07-11 | 2003-07-11 | Medication for treating cancer and chronic hepatitis B and its prepn. method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1985988B (en) * | 2005-12-19 | 2011-08-10 | 山东轩竹医药科技有限公司 | Novel medicine composition for treating hepatic diseases |
| CN101244075B (en) * | 2007-04-10 | 2011-09-14 | 上海医药工业研究院 | Application of astragaloside in preparing anti-hepatitis B virus medicaments |
| CN1977889B (en) * | 2005-12-05 | 2012-03-21 | 山东轩竹医药科技有限公司 | Medicinal composition of astragalus, salvia miltrorrhiza and oxymatrine, and its preparing method |
| CN110559327A (en) * | 2019-09-30 | 2019-12-13 | 杭州华缔集团有限公司 | Liver-protecting product and preparation method thereof |
-
2003
- 2003-07-11 CN CNA031397913A patent/CN1480192A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1977889B (en) * | 2005-12-05 | 2012-03-21 | 山东轩竹医药科技有限公司 | Medicinal composition of astragalus, salvia miltrorrhiza and oxymatrine, and its preparing method |
| CN1985988B (en) * | 2005-12-19 | 2011-08-10 | 山东轩竹医药科技有限公司 | Novel medicine composition for treating hepatic diseases |
| CN101244075B (en) * | 2007-04-10 | 2011-09-14 | 上海医药工业研究院 | Application of astragaloside in preparing anti-hepatitis B virus medicaments |
| CN110559327A (en) * | 2019-09-30 | 2019-12-13 | 杭州华缔集团有限公司 | Liver-protecting product and preparation method thereof |
| CN110559327B (en) * | 2019-09-30 | 2021-10-22 | 浙江华缔药业集团有限责任公司 | Liver-protecting product and preparation method thereof |
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